Radium-223 re-treatment from an international, prospective, open-label study in patients with castration-resistant prostate cancer and bone metastases

Date

09 Oct 2016

Session

Poster display

Presenters

Oliver Sartor

Citation

Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372

Authors

O. Sartor1, D. Heinrich2, N. Mariados3, M.J. Méndez Vidal4, D. Keizman5, C. Thellenberg Karlsson6, A. Peer7, G. Procopio8, S.J. Frank9, K.J. Pulkkanen10, E. Rosenbaum11, S. Severi12, J.M. Trigo Perez13, V. Wagner14, J. Garcia-Vargas15, R. Li16, L.T. Nordquist17

Author affiliations

  • 1 Medicine And Urology, Tulane Cancer Center, 70112 - New Orleans/US
  • 2 Oncology, Akershus University Hospital, Lorenskog/NO
  • 3 Radiation Oncology, Associated Medical Professionals of New York, PLLC, Syracuse/US
  • 4 Medical Oncology, Hospital Universitario Reina Sofía, Cordoba/ES
  • 5 Genitourinary Oncology, Meir Medical Center, Kfar Saba/IL
  • 6 Radiation Sciences, Cancer Center Norrlands University, Umea/SE
  • 7 Oncology, Rambam Medical Center, Haifa/IL
  • 8 Medical Oncology, Foundation IRCCS National Cancer Institute, Milano/IT
  • 9 Oncology, Hadassah Hebrew University Medical Center, Jerusalem/IL
  • 10 Oncology, Kuopio University Hospital, 70210 - Kuopio/FI
  • 11 Clinical Oncology, Rabin Medical Center–Davidoff Center, 49100 - Petach Tikva/IL
  • 12 Nuclear Medicine Therapeutic Unit, Romagnolo Scientific Institute for the Study and Care of Cancer—IRST IRCCS, Meldola/IT
  • 13 Medical Oncology, Hospital Universitario Virgen de la Victoria, Malaga/ES
  • 14 Global Clinical Development Oncology, Bayer Pharma AG, Basel/CH
  • 15 Global Clinical Oncology, Pharmaceuticals Division of Bayer, Whippany/US
  • 16 Global Research And Development Statistics, Pharmaceuticals Division of Bayer, Whippany/US
  • 17 Medical Oncology, GU Research Network, LLC, Omaha/US
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Background

Radium-223 (Ra-223) 50 kBq/kg IV (55 kBq/kg after NIST update) every 4 wk × 6 injections (inj) is indicated in symptomatic bone-metastatic castration-resistant prostate cancer (mCRPC) patients (pts) with no visceral metastases (mets). In an international prospective trial in mCRPC pts (NCT01934790), Ra-223 re-treatment (re-tx) after initial 6 inj was well tolerated, with very low radiologic bone progression rates (Sartor. ASCO GU 2016). Reported are safety and total alkaline phosphatase (ALP) and prostate-specific antigen (PSA) dynamics.

Methods

All pts had CRPC with bone mets and completed 6 Ra-223 inj with no bone progression during that initial tx. Pts had radiologic or clinical progression after initial Ra-223 tx, and adequate hematologic (heme) values. Pts who started subsequent anticancer tx must have progressed on the last anticancer tx. Concomitant agents (except cytotoxic) were allowed at investigator discretion. Addition of abiraterone and enzalutamide was not allowed during Ra-223 re-tx. Primary end point was safety; exploratory efficacy end points included times to ALP and PSA progression, and ALP and PSA response rates (≥30% decline from baseline).

Re-tx Study, N = 44 Re-tx Study, N = 44 Re-tx Study, N = 44 ALSYMPCA Ra-223 Arm, N = 600 ALSYMPCA Ra-223 Arm, N = 600 ALSYMPCA Ra-223 Arm, N = 600
Treatment-emergent adverse events* All Gr Gr 3 Gr 4 All Gr Gr 3 Gr 4
≥1 TEAE, % 93 41 7 93 35 9
Heme, %
Anemia 14 5 0 31 11 2
Thrombocytopenia 2 2 0 12 3 3
Neutropenia 0 0 0 5 2 1
Leukopenia 2 0 0 4 1 20% pts §ALSYMPCA intent-to-treat population n/N = pts with response/pts with valid lab assessment For ALSYMPCA, ALP response: ≥ 30% decline from baseline confirmed by a second measurement ≥4 wk later; PSA response: ≥ 30% decline from baseline # ALSYMPCA: End of tx (4 wks after last inj) **N = safety population; pts with no valid postbaseline lab assessment counted as nonresponders; database cutoff date was June 11, 2015 NA = not applicable

Results

Of 44 Ra-223 re-tx pts, 29 (66%) received all 6 inj. Median time from last inj of initial Ra-223 tx was 6 mo. There were no marked alterations in tx-emergent adverse event (TEAE) incidence vs ALSYMPCA (Table) and no grade 4 or 5 heme TEAEs; 3 (7%) re-tx pts had grade 3 or 4 tx-related TEAEs. Maximum follow-up times for ALP and PSA progression were 12.8 and 11.4 mo, respectively. Median time to ALP progression was not reached. Median time to PSA progression was 2 mo. ALP and PSA response rates at wk 12, 24, and any time before database cutoff are reported (Table). ALP, PSA, and heme lab values will be reported.

Conclusions

Ra-223 re-tx was well tolerated, with minimal heme toxicity and ALP and PSA profiles similar to those of ALSYMPCA.

Clinical trial identification

NCT01934790

Legal entity responsible for the study

Pharmaceuticals Division of Bayer

Funding

Pharmaceuticals Division of Bayer

Disclosure

O. Sartor: Consultant or advisory role for Astellas, Bavarian Nordic, Bayer, Bellicum, Biscayne, Johnson & Johnson, Medivation, Oncogenex, Sanofi, Algeta, Aragon, and Pfizer; research funding from Bayer, Johnson & Johnson, Progenics, Sanofi, Algeta, and Takeda.

D. Heinrich: Honoraria from and consultant or advisor for Bayer, Johnson & Johnson, and Astellas; research funding from Bayer, Johnson & Johnson, BMS, and Aragon Pharmaceuticals.

N. Mariados: Stock or ownership interest in and travel, accommodations, expenses from Augmenix; honoraria from and speakers bureau for Bayer.

M.J. Méndez Vidal: Consulting or advisory role for Janssen-Cilag, Pfizer, Astellas, GlaxoSmithKline, Sanofi, and Bayer; travel, accommodations, expenses from Janssen-Cilag, Pfizer, Astellas, and GlaxoSmithKline.

D. Keizman: Consulting or advisory role for, honoraria from, and travel, accommodations, and expenses from Bayer, Pfizer, Sanofi, and Janssen Oncology.

C. Thellenberg Karlsson: Consulting or advisory role for Bayer and Sanofi.

G. Procopio: Consulting or advisory role for Janssen, Novartis, and Bayer; honoraria from Astellas and Janssen.

S. Severi: Speakers bureau for Bayer.

V. Wagner: Was employed by Merck; is now employed by Bayer; stock or other ownership in Bayer, Merck, and Amgen.

J. Garcia-Vargas: Employed by Bayer; travel, accommodations, expenses from Bayer.

R. Li: Employed by Bayer.

All other authors have declared no conflicts of interest.

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